Figure 1.

Feedback produces stem cell and transit amplifying cell behaviors. A two-stage cell lineage is shown, in which cells of type 0 and type 1 divide (at rates v₀ and v₁, respectively), and produce progeny with an intrinsic probability (p₀ or p₁, respectively) of remaining at the same lineage stage (as opposed to differentiating to the next one). Cell type 2 is terminally differentiated, and dies (or is shed) at rate d. As long as p₀ > 0.5, any negative feedback (schematized by solid red lines, and quantified by parameters g₁ and g₂) from cell type 2 onto p₀ forces the system to reach a self-maintaining steady state. If there is feedback onto both p₀ and p₁, the quantitative details determine whether cell type 0 behaves like a stem cell and cell type 1 like a transit amplifying cell; or whether cell type 1 behaves like a stem cell and cell type 0 goes extinct. If feedback also slows cell division (for example, v₀, dashed red line), more complex system behaviors may occur (for example, in which cell type 1 normally fulfills most stem cell functions, with cell type 0 remaining quiescent except following tissue injury, when it transiently 'reawakens'). For further details see [7,14,17].